ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang （QLHQT） on nonalcoholic steatohepatitis （NASH）. MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling， mice were randomly assigned to the model group， low-， medium-， and high-dose QLHQT groups （0.51， 1.02， and 2.04 g·kg^-1）， and a positive control metformin group， with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C）， as well as hepatic TC， TG， and LDL-C contents， were determined by biochemical assays. Hematoxylin-eosin （HE） staining and oil red O staining were used to evaluate liver histopathology and lipid deposition， respectively. Flow cytometry， enzyme-linked immunosorbent assay （ELISA）， and Real-time polymerase chain reaction （Real-time PCR） were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group， body weight and serum and hepatic levels of TC， TG， and LDL-C were significantly increased in the model group （P<0.01）. Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm， accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased， whereas the proportion of CD206-positive cells was markedly decreased （P<0.05）. Hepatic inducible nitric oxide synthase （iNOS） levels and tumor necrosis factor-α （TNF-α） mRNA expression were significantly increased， while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased （P<0.01）. The protein expression levels of Toll-like receptor 4 （TLR4）， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） in the liver were significantly increased （P<0.01）. Compared with the model group， body weight was reduced in the high-， medium-， and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC， TG， and LDL-C levels were significantly decreased （P<0.01）. Liver histopathology showed alleviated hepatic lipid deposition， with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased， whereas the proportions of CD206-positive cells were significantly increased in the high-， medium-， and low-dose QLHQT groups （P<0.05）. Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased （P<0.01）， whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased （P<0.01）. The hepatic protein expression levels of TLR4， TRAF6， and MyD88 were significantly decreased， while signal transducer and activator of transcription 6 （STAT6） phosphorylation was significantly increased （P<0.05， P<0.01）. There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice， and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.

ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang （QLHQT） on nonalcoholic steatohepatitis （NASH）. MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling， mice were randomly assigned to the model group， low-， medium-， and high-dose QLHQT groups （0.51， 1.02， and 2.04 g·kg^-1）， and a positive control metformin group， with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C）， as well as hepatic TC， TG， and LDL-C contents， were determined by biochemical assays. Hematoxylin-eosin （HE） staining and oil red O staining were used to evaluate liver histopathology and lipid deposition， respectively. Flow cytometry， enzyme-linked immunosorbent assay （ELISA）， and Real-time polymerase chain reaction （Real-time PCR） were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group， body weight and serum and hepatic levels of TC， TG， and LDL-C were significantly increased in the model group （P<0.01）. Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm， accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased， whereas the proportion of CD206-positive cells was markedly decreased （P<0.05）. Hepatic inducible nitric oxide synthase （iNOS） levels and tumor necrosis factor-α （TNF-α） mRNA expression were significantly increased， while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased （P<0.01）. The protein expression levels of Toll-like receptor 4 （TLR4）， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） in the liver were significantly increased （P<0.01）. Compared with the model group， body weight was reduced in the high-， medium-， and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC， TG， and LDL-C levels were significantly decreased （P<0.01）. Liver histopathology showed alleviated hepatic lipid deposition， with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased， whereas the proportions of CD206-positive cells were significantly increased in the high-， medium-， and low-dose QLHQT groups （P<0.05）. Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased （P<0.01）， whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased （P<0.01）. The hepatic protein expression levels of TLR4， TRAF6， and MyD88 were significantly decreased， while signal transducer and activator of transcription 6 （STAT6） phosphorylation was significantly increased （P<0.05， P<0.01）. There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice， and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.

Objective:To explore the current status of clinical trial registration for TCM treatment of heart failure.Methods:The clinical trials of TCM in the treatment of heart failure registered by China Clinical Trial Registry (ChiCTR) from the establishment of the database to June 30, 2024 were retrieved. Excel 2019 was used to input data and register time, registration area and institution, registration center and sample size, funding source, intervention measures, outcome indicators, random methods and blind methods were used for frequency analysis.Results:A total of 71 clinical trials of TCM in the treatment of heart failure in China were included, involving 13 provincial-level administrative regions. There were 39 clinical trial institutions participating in the registration, with Shanghai (16 items), Beijing (15 items), and Tianjin (12 items) ranking at the top in terms of registration numbers; the funding mainly relied on local finances, followed by national finances and hospital grants; in the registered projects, interventional studies accounted for the majority, mainly grouped through random number table methods, and only a small number of trials used blinding methods, with single-center participation being the norm; in terms of intervention measures, mainly Chinese patent medicines were used, while TCM decoctions were used less frequently. Outcome indicators were mainly efficacy indicators such as biochemical results and echocardiography, lacking monitoring of safety indicators.Conclusions:The number of clinical trial registrations for TCM in the treatment of heart failure in China is relatively small, but it shows a trend of increasing year by year. In terms of intervention measures, the treatment methods are also continuously enriching. However, there are still issues with clinical trials of TCM for the prevention and treatment of heart failure, such as insufficient awareness of registration among researchers, unbalanced regional and institutional distribution, and the need for improvement in the use of randomization and blinding methods.

The elimination of biofilms is a crucial step in controlling hospital-acquired infections.Once biofilms colonize luminal instruments,it is difficult to remove them using traditional disinfection methods.Conventional disinfection approaches now face a series of challenges,including microbial resistance,corrosiveness,cytotoxicity,residual disinfection byproducts,and environmental pollution.Therefore,developing novel disinfection technologies specifically targeting biofilm removal is vitally important.New disinfection technologies,such as slightly acidic electrolyzed water,plasma technology,surface modification techniques,nanomaterial-based disinfection,bacteriophage disinfection,and enzymatic disinfection,are constantly emerging.These technologies exhibit excellent performance against biofilms by leveraging the synergistic effects of multiple mechanisms,including the reactive oxygen species(ROS)burst,photocatalytic oxidation,physical disruption,and biological targeting.This review summarizes the characteristics,underlying mechanisms,and potential application scenarios of these novel disinfection technologies,with a particular focus on their effects against biofilms formed by common pathogenic bacteria on surfaces in hospital settings.It aims to provide a reference basis for the practical application and translation of these disinfection technologies and the development of new disinfection strategies.

Objective To investigate the damage of pepsin to the mucosal epithelium of the pharynx under a-cidic and non-acidic conditions,and to provide new ideas for the treatment of refractory laryngopharyngeal reflux diseases.Methods A total of 30 healthy guinea pigs were selected and randomly divided into 3 groups(with 10 in each group).The animals in group A were perfused with 0.3％pepsin+hydrochloric acid solution(pH=2),the animals in group B were perfused with 0.3％pepsin+sterilized distilled water(pH=7),and the animals in group C were perfused with sterilized distilled water(pH=7).After 14 days of perfusion,the mucosal tissues of the post-cyclic area were examined by HE staining,immunohistochemistry,and transmission electron microscopy to detect the degree of inflammatory cell infiltration,the expression of occludin and claudin-3 proteins,the degree of epithelial cell gap widening,and also to analyze the changes of cell submicroscopic structure under electron microscopy.Re-sults ① The submucosal leukocyte count was 28.61±7.10 in group A,29.89±7.04 in group B,and 7.81±1.40 in group C.Compared with group C,the leukocyte count was higher in group A and group B(P＜0.05).② Com-pared with group C,both occludin and claudin-3 protein expression were downregulated in group A(P＜0.05),compared with group C,the difference between occludin and claudin-3 protein expression in group B was not statisti-cally significant(P＞0.05).③ Under electron microscopy,the mucosal epithelial cell gap was widened,the mito-chondria was swollen and the cristae was degraded in group A.In group B,there was no widening of the mucosal epithelial cell gap,but the mitochondria in the cytoplasm was swollen and the cristae was degraded,and there was no widening of mucosal epithelial cell gap and the morphological markers of mitochondria were clear in group C.Conclusion Under non-acidic conditions,pepsin still can cause inflammatory changes and mitochondrial damage in the mucosal epithelium of the pharynx.

Objective:To analyze the clinical features of pachydermoperiostosis (PDP) and improve its diagnostic level.Methods:A retrospective analysis was conducted on the clinical data of four patients with PDP treated at Sun Yat-sen Memorial Hospital, Sun Yat-sen University from 2015 to 2023, including clinical manifestations, laboratory tests, imaging examinations, and genetic testing results.Results:All four patients were male with an average onset age of 15 years old (ranging from 9 to 18 years old). One patient′s uncle had PDP, and another patient′s parents were consanguineous, though neither parent showed signs of PDP. All four patients exhibited clubbing, skin thickening, and acne; three had frontal bossing and deepened nasolabial folds; two showed scalp sulci changes on head MRI, and all had periosteal thickening of the phalanges visible on X-ray. One patient accompanied with hypokalemic nephropathy, and another had gastric ulcer. One patient underwent whole exome sequencing test which revealed a homozygous mutation, SLCO2A1 gene c.1406C>T, leading to a protein change p.Pro469Leu. Computational tools REVEL, SIFT, and Polyphen2 predicted this variant as deleterious.Conclusion:In addition to skin thickening, frontal bossing, scalp sulci changes, clubbing, and periosteal proliferation, patients with PDP may also present with hypokalemic nephropathy and gastric ulcer. The SLCO2A1 gene c.1406C>T mutation may be pathogenic.

Objective:To discuss the effect of sericin on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/nuclear factor-κB(NF-κB)signaling pathway and apoptosis in the streptozotocin(STZ)-damaged INS-1 cells,and to clarify its mechanism.Methods:The INS-1 cells were cultured with complete medium containing 0,0.1,0.3,1.0,3.0,and 10.0 μmol·L-1 Akt1 inhibitor A-674563,10 mmol·L-1 STZ,and 600 mg·L-1 sericin,and divided into 0,0.1,0.3,1.0,3.0,and 10.0 μmol·L-1 A-674563 groups,and the control group(complete medium without drugs)was set up.Cell counting kit-8(CCK-8)method was used to detect the survival rates of the INS-1 cells,and the half-maximal inhibitory concentration(IC50)value was calculated to determine the optimal inhibitory concentration of A-674563,which was further verified by Western blotting method.The INS-1 cells were divided into normal control group(complete medium),model group(10 mmol·L-1 STZ+complete medium),and low,medium,and high doses of sericin groups(10 mmol·L-1 STZ+150 mg·L-1 sericin+complete medium,10 mmol·L-1 STZ+300 mg·L-1 sericin+complete medium,and 10 mmol·L-1 STZ+600 mg·L-1 sericin+complete medium).CCK-8 method was used to detect the survival rates of the INS-1 cells in various groups to determine the optimal concentration of sericin.Additionally,the INS-1 cells were divided into normal control group(complete medium),model group(10 mmol·L-1 STZ+complete medium),sericin group(10 mmol·L-1 STZ+600 mg·L-1 sericin+complete medium),and A-674563 group(10 mmol·L-1 STZ+600 mg·L-1 sericin+0.3 μmol·L-1 A-674563+complete medium).Flow cytometry was used to detect the apoptotic rates of the INS-1 cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Akt1,NF-κB,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)mRNA in the INS-1 cells in various groups;Western blotting method was used to detect the expression levels of phosphorylated Akt1(p-Akt1)and NF-κB proteins in the INS-1 cells in various groups;enzyme linked immunosorbent assay(ELISA)method was used to detect the levels of TNF-α and IL-6 in the INS-1 cells in various groups.Results:The survival rates of the INS-1 cells in control group was 100.00%±0.00%;in 0,0.1,0.3,1.0,3.0,and 10.0 μmol·L-1 A-674563+10 mmol·L-1 STZ+600 mg·L-1 sericin+complete medium groups,which were 82.50%±2.28%,69.47%±1.94%,51.51%±1.74%,38.94%±1.57%,24.79%±1.14%,and 19.85%±1.03%,respectively.The IC?? value of A-674563 for INS-1 cells was 0.3 μmol·L-1,and 0.3 μmol·L-1 A-674563 was selected for subsequent experiments.Compared with 0 μmol·L-1 A-674563,the expression level of p-Akt1 protein in the INS-1 cells after treated with 0.3 μmol·L-1 A-674563+10 mmol·L-1 STZ+600 mg·L-1 sericin+complete medium was significantly decreased(P<0.05).The CCK-8 results showed that compared with normal control group,the survival rate of the INS-1 cells in model group was significantly decreased(P<0.05);compared with model group,the survival rates of the INS-1 cells in low,medium,and high doses of sericin groups were significantly increased(P<0.05);compared with low and medium doses of sericin groups,the survival rate of the INS-1 cells in high dose of sericin group was significantly increased(P<0.05).Thus,600 mg·L-1 sericin was selected for subsequent experiments.The CCK-8 results showed that compared with normal control group,the survival rate of the INS-1 cells in model group was significantly decreased(P<0.05);compared with model group,the survival rate of the INS-1 cells in sericin group was significantly increased(P<0.05);compared with sericin group,the survival rate of the INS-1 cells in A-674563 group was significantly decreased(P<0.05).The flow cytometry results showed that compared with normal control group,the apoptotic rate of the INS-1 cells in model group was significantly increased(P<0.05);compared with model group,the apoptotic rate of the INS-1 cells in sericin group was significantly decreased(P<0.05);compared with sericin group,the apoptotic rate of the INS-1 cells in A-674563 group was significantly increased(P<0.05).The RT-qPCR results showed that compared with normal control group,the expression level of Akt1 mRNA in the INS-1 cells in model group was significantly decreased(P<0.05);compared with model group,the expression levels of Akt1 mRNA in the INS-1 cells in low,medium,and high doses of sericin groups were significantly increased(P<0.05);compared with low and medium doses of sericin groups,the expression level of Akt1 mRNA in the INS-1 cells in high dose of sericin group was significantly increased(P<0.05).Compared with normal control group,the expression levels of NF-κB,TNF-α,and IL-6 mRNA in the INS-1 cells in model group were significantly increased(P<0.05);compared with model group,the expression levels of NF-κB,TNF-α,and IL-6 mRNA in the INS-1 cells in sericin group were significantly decreased(P<0.05);compared with sericin group,the expression level of NF-κB mRNA in the INS-1 cells in A-674563 group was significantly increased(P<0.05).The Western blotting results showed that compared with normal control group,the expression level of p-Akt1 protein in the INS-1 cells in model group was significantly decreased(P<0.05);compared with model group,the expression levels of p-Akt1 protein in the INS-1 cells in low,medium,and high doses of sericin groups were significantly increased(P<0.05);compared with low and medium doses of sericin groups,the expression level of p-Akt1 protein in the INS-1 cells in high dose of sericin group was significantly increased(P<0.05).Compared with normal control group,the expression level of NF-κB protein in the INS-1 cells in model group was significantly increased(P<0.05);compared with model group,the expression level of NF-κB protein in the INS-1 cells in sericin group was significantly decreased(P<0.05);compared with sericin group,the expression level of NF-κB protein in the INS-1 cells in A-674563 group was significantly increased(P<0.05).The ELISA results showed that compared with normal control group,the levels of TNF-α and IL-6 in the INS-1 cells in model group were significantly increased(P<0.05);compared with model group,the levels of TNF-α and IL-6 in the INS-1 cells in sericin group were significantly decreased(P<0.05);compared with sericin group,the levels of TNF-α and IL-6 in the INS-1 cells in A-674563 group were significantly increased(P<0.05).Conclusion:Sericin alleviates the PI3K/Akt/NF-κB signaling pathway-mediated inflammatory response and apoptosis by targeting Akt1,exerting a protective effect against STZ-induced damage in INS-1 cells.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.